Aim: This research explores how myocyte-specific deletion of the vitamin D receptor (mVDR) affects skeletal muscle function, structure, and regenerative capacity following induced injury.
Methods: Male mVDR mice (n = 15) were generated by crossing floxed vitamin D receptor (VDR) mice with human skeletal actin-Cre mice, and their male floxed littermates were used as controls (n = 13). Muscle injury was induced by intramuscular injection of 25 µg/kg Notexin into the right tibialis anterior (TA), with saline injected contralaterally as control. Body weight, grip strength, treadmill endurance, and voluntary wheel-running were assessed. TA and quadriceps were collected for histological analysis.
Results: Body weight, endurance capacity, and voluntary running activity did not differ significantly between mVDR and floxed controls (FC). Grip strength was significantly reduced in mVDR mice 26 days post-notexin injury (~6.5% decrease; p < 0.01) compared to FC. TA weight was 25% lower following injury in mVDR relative to their own saline-treated limb (p = 0.045), but remained 18% heavier than injured FC. Hematoxylin & eosin staining of mVDR notexin-treated muscles revealed a marked increase in centralised nuclei (43.4% mVDR vs. 20.7% FC) and slightly greater cross-sectional diameter of myofibres (27.49 µm mVDR vs 26.18 µm FC), as well as prominent signs of inflammation, angulated fibres, and adipocyte infiltration. Sirius Red staining demonstrated enhanced collagen deposition in mVDR muscles (7.7% mVDR vs. 4.8% FC), indicating increased fibrosis.
Conclusion: Myocyte VDR deletion alters skeletal muscle regeneration following injury. Further investigation of gene expression profiles and muscle fibre-type composition is needed to elucidate the underlying molecular mechanisms.